Purpose: DERC Mouse Genetics Core. This Core laboratory generates mutant mice for use by DERC investigators. Components: 1. Transgenic mouse production. Mice are produced by traditional microinjection of plasmid DNA in a variety of backgrounds including NOD. Reliable methods for generating transgenic mice with bacterial artificial chromosomes (BACs) and lentiviruses also were developed within the Core. 2. BAC recombineering. The Core assists DERC investigators by generating transgenic or targeting vectors from BACs by homologous recombination in E. coll. The BACs then are used for efficient transgenesis or targeted mutations in ES cells. 3. Gene targeting. The Core performs gene targeting with plasmid or BAC DNA in mouse ES cells and injects mutant ES cells into mouse blastocysts. 4. Rederivation and cryopreservation. The Core performs embryo transfers for rederivation of imported and/or infected strains of mice into the pathogen-free mouse facility, and mouse embryo cryopreservation for line maintenance. Benefits to DERC Community: The Core accelerates progress towards the overall programmatic goals of the UCSF DERC by making advanced genetic technologies available to the broad diabetes research community. Cutting-edge technologies are conducted with high efficiency by skilled technicians. The maintenance of standing cell and mouse lines ensure immediate availability at no start-up costs. The Core provide an important information and training function by keeping participants abreast of the latest advances in mouse genetic technologies. Technology Development: An important function of the Core is to acquire, develop and validate new mouse genetic technologies. DERC support enables the development of capabilities of particular interest to diabetes-oriented studies.